Research ReportMidbrain dopamine neurons in Parkinson׳s disease exhibit a dysregulated miRNA and target-gene network

- We analyzed gene and miRNA expression profiles in postmortem dopamine neurons in PD.
- DA neurons in PD have dysregulated miRNA expression profiles that are sex-specific.
- miRNAs are associated with dysregulated target-genes in PD DA neurons.
- miRNAs are involved in dysregulated pathways that are linked to PD pathogenesis.
- Dysregulated miRNA/gene-target expression networks in PD may be sex-specific.

The degeneration of substantia nigra (SN) dopamine (DA) neurons in sporadic Parkinson׳s disease (PD) is characterized by disturbed gene expression networks. Micro(mi)RNAs are post-transcriptional regulators of gene expression and we recently provided evidence that these molecules may play a functional role in the pathogenesis of PD. Here, we document a comprehensive analysis of miRNAs in SN DA neurons and PD, including sex differences. Our data show that miRNAs are dysregulated in disease-affected neurons and differentially expressed between male and female samples with a trend of more up-regulated miRNAs in males and more down-regulated miRNAs in females. Unbiased Ingenuity Pathway Analysis (IPA) revealed a network of miRNA/target-gene associations that is consistent with dysfunctional gene and signaling pathways in PD pathology. Our study provides evidence for a general association of miRNAs with the cellular function and identity of SN DA neurons, and with deregulated gene expression networks and signaling pathways related to PD pathogenesis that may be sex-specific.